AI Article Synopsis
- TGF-β is a cytokine that influences various cellular processes, and its effects on cholangiocytes (bile duct cells) are not well understood; this study investigates how TGF-β impacts cholangiocyte behavior.
- Results showed that TGF-β treatment leads to reduced cholangiocyte proliferation and causes them to enter a resting phase (G0/G1) in the cell cycle, suggesting a halt in their growth.
- Proteomic analysis identified four key proteins related to calcium regulation that were downregulated due to TGF-β, indicating that the cytokine may disrupt calcium homeostasis and affect cellular compartments like the plasma membrane and endoplasmic reticulum.
Article Abstract
TGF-β is a cytokine implicated in multiple cellular responses, including cell cycle regulation, fibrogenesis, angiogenesis and immune modulation. In response to pro-inflammatory and chemotactic cytokines and growth factors, cholangiocytes prime biliary damage, characteristic of cholangiopathies and pathologies that affect biliary tree. The effects and signaling related to TGF-β in cholangiocyte remains poorly investigated. In this study, the cellular response of human cholangiocytes to TGF-β was examined. Wound-healing assay, proliferation assay and cell cycle analyses were used to monitor the changes in cholangiocyte behavior following 24 and 48 h of TGF-β stimulation. Moreover, proteomic approach was used to identify proteins modulated by TGF-β treatment. Our study highlighted a reduction in cholangiocyte proliferation and a cell cycle arrest in G0/G1 phase following TGF-β treatment. Moreover, proteomic analysis allowed the identification of four downregulated proteins (CaM kinase II subunit delta, caveolin-1, NipSnap1 and calumin) involved in Ca homeostasis. Accordingly, Gene Ontology analysis highlighted that the plasma membrane and endoplasmic reticulum are the cellular compartments most affected by TGF-β. These results suggested that the effects of TGF-β in human cholangiocytes could be related to an imbalance of intracellular calcium homeostasis. In addition, for the first time, we correlated calumin and NipSnap1 to TGF-β signaling.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033039 | PMC |
| http://dx.doi.org/10.3390/biology11040566 | DOI Listing |
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